There is increasing evidence to support the hypothesis that somatic cell mutations are causally related to chemical carcinogenesis and that DNA repair processes recognize and repair lesions caused by carcinogens. We have reported that the frequency of mutations induced in cells derived from xeroderma pigmentosum (XP) patients (who are prone to sunlight-induced skin cancer and defective in excision repair of UV light-induced DNA damage) is significantly higher than in normal cells. Our more recent studies indicate that a similar result occurs with chemical carcinogens as the DNA-damaging agents. Although studies have been done to detect, characterize, and quantitate DNA repair following carcinogen attack, few have directly examined the effect of DNA repair processes on the induction of mutations and correlated this with the number and types of DNA adducts formed. The fundamental purpose of this research is to examine the effect of DNA repair on the induction of mutations by selected carcinogenic agents in normal human cells and in cells derived from persons with genetic predisposition to caner (classical and variant XP's; ataxia telangiectasia; Fanconi's anemia; etc.). We will: (1) Investigate the effect of DNA excision repair processes acting on chemical agents induce "UV-like" repair, "gamma-ray-like" repair, cross-links, etc. (2) Determine the effect of DNA post-replication repair of such damage; and (3) Determine, using radioactively-labeled carcinogens and sensitive biochemical techniques, the number and kinds of DNA-carcinogen adducts that correlate (4) Compare the effects of "simulated sunlight" with those found for 254 nm and (5) Compare the effects of carcinogens in human epithelial cells with those observed in fibroblasts. A basic understanding of the effect of cellular repair processes on the mutagenic action of carcinogens in human cells is essential for understanding their mechanisms of action.